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Review
. 2025 Apr 15;14(8):2710.
doi: 10.3390/jcm14082710.

Association Between the Use of Oral Contraceptives and the Development of Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

Annalisa Marino  1   2 , Damiano Currado  1   2 , Onorina Berardicurti  1   2 , Marta Vomero  2 , Lyubomyra Kun  2 , Letizia Pia Di Corcia  2 , Erika Corberi  2 , Francesca Trunfio  2 , Francesca Saracino  2 , Ludovica Lamberti  2 , Leonardo Frascà  2 , Angelo Battista  2 , Marta Alfano  2 , Manuela Pietramale  2 , Silvia Schiavone  2 , Roberto Giacomelli  1   2 , Luca Navarini  1   2
Affiliations
Review

Association Between the Use of Oral Contraceptives and the Development of Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

Annalisa Marino et al. J Clin Med. .

Abstract

Background: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that significantly impacts quality of life, particularly among women. Previous studies have suggested that oral contraceptive (OC) use may influence RA risk, but conflicting findings from earlier meta-analyses necessitate an updated analysis incorporating more recent data. Methods: We conducted a systematic review and meta-analysis of observational studies on OC use and RA risk by searching MedLine (via PubMed), Scopus, and Cochrane Databases up to September 2024. Results: Our analysis demonstrated that current or prior use of OCs is associated with a statistically significant reduction in RA risk (OR 0.80, 95% CI 0.70-0.91). In contrast, the associations for current use (OR 0.59, 95% CI 0.34-1.02) and past use (OR 0.83, 95% CI 0.69-1.01) were less definitive, likely due to substantial heterogeneity among studies. Cumulative meta-analysis revealed a modest temporal trend toward a protective effect of OC use. Conclusions: This meta-analysis supports a protective association between current or prior OC use and the development of RA, highlighting the potential role of hormonal factors in RA pathogenesis.

Keywords: hormonal factors; meta-analysis; oral contraceptives; rheumatoid arthritis; risk assessment.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
PRISMA 2020 flow diagram showing an overview of the study selection process. Source: [15].
Figure 2
Figure 2
Forest plots of odds ratio (OR) of ever having used OCs and RA risk [19,20,21,22,23,24,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40].
Figure 3
Figure 3
Cumulative analysis of the use of OCs at any point and RA risk [19,20,21,22,23,24,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40].
Figure 4
Figure 4
Forest plots of odds ratio (OR) for current use of OCs and RA risk [22,26,29,30,36,41,42,43].
Figure 5
Figure 5
Cumulative analysis of current use of OCs and RA risk [22,26,29,30,36,41,42,43].
Figure 6
Figure 6
Forest plot of past use of OCs and RA risk [22,26,43,44,45,46].
Figure 7
Figure 7
Cumulative analysis of past use of OCs and RA risk [22,26,43,44,45,46].
See this image and copyright information in PMC

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